Enantioselective and Diastereoselective C-H Alkylation of Benzamides: Synergized Axial and Central Chirality via a Single Stereodetermining Step

In this report, distally disposed axial and central chirality has been installed in a synergistic fashion via rhodiumcatalyzed C-H alkylation of benzamides using N-arylmaleimide as the alkylating reagent, in which the enantio- and diastereo-determining steps are merged into a single one. The coupling system features mild reaction conditions, broad substrate scope, and excellent enantio- and diastereoselectivity. The chiral induction has been enabled by judicious choice of a chiral rhodium cyclopentadienyl catalyst that serves to control both the orientation of the olefin unit and the prochiral C-N bond.

Automated summary

This report describes a method for introducing distally disposed axial and central chirality via rhodium-catalyzed C-H alkylation of benzamides using N-arylmaleimide as the alkylating reagent. The process features excellent enantio- and diastereoselectivity, broad substrate scope, and mild reaction conditions. Chiral induction is achieved through the judicious choice of a chiral rhodium cyclopentadienyl catalyst.